Neglected tropical diseases

Monitoring of Drug Efficacy in Large Scale Treatment Programmes for Human Helminthiasis

Working groups and update on progress since October 2007

Soil-transmitted helminthiasis (STH)
Coordinator: Jozef Vercruysse. Members: Marco Albonico, Jerzy Behnke, Donald Bundy, Gerald Coles, Tom Churcher, Lesley Drake, Peter Hotez, Ray Kaplan, Katherine Woo, Andrew Kotze, James McCarthy, Roger Prichard, Georg von Samson-Himmelstjerna, Michael Wilson

This working group has since written a position paper, summarizing in detail what is currently known about anthelminthic drug efficacy in human soil-transmitted helminthiasis, and making recommendations for: (1) the most appropriate coprological methods to be used to monitor the efficacy of anthelmintics used in control programmes; (2) the establishment of a checklist of confounding factors that may affect anthelmintic efficacy; (3) Standard Operating Procedures (SOPs), i.e. the appropriate design of studies to monitor efficacy of anthelmintics by Faecal Egg Count Reduction Tests (FECRT), including the statistical analysis to be used for the FECRT; (5) the (biological) laboratory methods to be considered to evaluate and confirm Anthelminthic Resistance (AR) for human STH, including the research needed on improved (molecular) tools for determining the presence of AR; and (6) the algorithms and referral processes needed for monitoring AR in endemic areas.

Studies have been planned to field-test these protocols in multiple settings with various history of large scale benzimidazole use. These field studies will be carried out during the second half of 2008 and should allow to validate the proposed methodologies for the monitoring of drug efficacy in large-scale treatment programmes for human infections with STH. They are also expected to shed light on threshold FECR values that should trigger the need for laboratory confirmation, and laboratory results that are conclusive of AR.

Onchocerciasis/ Lymphatic Filariasis
Coordinator: Uche Amazigo. Members: Hans Remme, Patrick Lammie, members of the Technical Consultative Committee of APOC (TCC/APOC), members of the Technical Advisory Group for the Elimination of Lymphatic Filariasis (TAG-ELF).

This working group has since organized a meeting, Geneva, 3-5 March 2008 in order to: (1) carry out a detailed analysis of all published reports on ivermectin efficacy in order to comprehensively assess the evidence of ivermectin resistance; (2) plan for follow-up studies in Ghana in order to assess confounding factors that may have affected the reported reduction in ivermectin efficacy stated in a recent Lancet article (Osei-Atweneboana et al., 2007); (3) formulate clear definitions of ivermectin resistance; (4) pèrepare guidelines for the monitoring of ivermectin efficacy in onchocerciasis (and lymphatic filariasis) control; and (5) suggest new sensitive tools for the early detection of drug resistance and define procedures for developing these tools.

The field studies in Ghana are also expected to be carried out during the second half of 2008, and a follow-up meeting has been planned to specifically plan for the development of molecular markers to survey for ivermectin resistance (Geneva, 16-17 June 2008).

Coordinator: Paul Hagan. Members: Tim Anderson, Donato Cioli, Rodrigo Correa-Oliveira, Mike Doenhoff, Narcis Kabatereine, Frank Richards, Joanne Webster

No update on progress received so far.

Coordinator: Tim Geary. Members: Nilanthi De Silva, Katherine Woo, Janis Lazdins-Helds, James McCarthy

This working group has prepared a draft position paper highlighting unresolved issues in the pharmacology of the anthelminthic drugs currently used in large scale control programmes, and proposing avenues to improve their efficacy and prevent or delay the development of resistance.

Indeed, although it is important to develop new anthelminthic compounds of a totally different family than existing anthelminthics, there is still ample room to reassess the pharmacology of existing anthelminthics in order to optimize their use, alone or in combination. Such improvements in the use of current products could require action with varying complexity, timelines and costs, such as: (1) human pharmacology (PK drug interaction) studies of co-administration of currently used drugs in humans for helminths, (2) the development of new formulations of available anthelminthics used in humans; (3) the development of fixed dose formulations; (4) the development of anthelminthic drugs currently used in veterinary field but not in humans.

The working group also addressed the issue of understanding drug mechanism of action to develop tools for the early detection of AR, which will require more basic research in molecular biology, biochemistry, and animal models.